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GUIDELINES
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INTRODUCTION
The incidence of multiple pregnancy is rising, mainly
due to delayed childbirth and advanced maternal age at
conception and the resultant widespread use of assisted
reproduction techniques1 . The twin birth rate increased
by just under 70% between 1980 (19 per 1000 live births)
and 2006 (32 per 1000 live births)2 .
Twin pregnancy is associated with a high risk of perinatal mortality and morbidity3 6 . In 2009, the associated
stillbirth rate was 12 per 1000 twin births and 31 per
1000 triplet and higher-order multiple births, compared
with five per 1000 singleton births7,8 . Preterm birth prior
to 37 weeks gestation occurs in up to 60% of multiple
pregnancies, contributing to the increased risk of neonatal
mortality (65% of neonatal deaths among multiple births
are preterm, compared with 43% of neonatal deaths in
singletons) and long-term morbidity9 12 . Of course, such
complications rise with a reduction in gestational age
OUTLINE/SCOPE
ISUOG GUIDELINES
248
RECOMMENDATIONS
Dating of twin pregnancy
Twin pregnancies should ideally be dated when the
crownrump length (CRL) measurement is between 45
and 84 mm (i.e. 11 + 0 to 13 + 6 weeks of gestation)
(GRADE OF RECOMMENDATION: D).
In pregnancies conceived spontaneously, the larger of
the two CRLs should be used to estimate gestational
age (GRADE OF RECOMMENDATION: C).
Other studies have recommended the use of the smaller
CRL or the mean CRL, which takes into account both
fetuses13 15 . The disadvantage of using the smaller CRL
is the potential of the operator believing that the larger
twin is large-for-gestational age, and therefore being
falsely reassured that the smaller twin is still growing
appropriately. The most common practice is to use the
ISUOG Guidelines
larger CRL. If the woman presents after 14 weeks gestation, the larger head circumference should be used1 . Twin
pregnancies conceived via in-vitro fertilization should be
dated using the oocyte retrieval date or the embryonic age
from fertilization (EVIDENCE LEVEL: 2+).
ISUOG Guidelines
249
Lambda sign
T sign
Figure 1 Ultrasound images in the first trimester of: (a) a dichorionic diamniotic twin pregnancy, in which the twins are separated by a thick
layer of fused chorionic membranes; (b) a monochorionic diamniotic twin pregnancy, in which the twins are separated by only two thin
amniotic layers.
ISUOG Guidelines
250
Dichorionic twin pregnancy
1114 weeks
Dating, labeling
Chorionicity
Screening for trisomy 21
2022 weeks
Detailed anatomy
Biometry
Amniotic fluid volume
Cervical length
2426 weeks
2830 weeks
3234 weeks
1114 weeks
16 weeks
Fetal growth, DVP
UA-PI
18 weeks
20 weeks
24 weeks
26 weeks
Delivery
28 weeks
Detailed anatomy
Biometry, DVP
UA-PI, MCA-PSV
Cervical length
22 weeks
3637 weeks
Dating, labeling
Chorionicity
Screening for trisomy 21
32 weeks
34 weeks
36 weeks
ISUOG Guidelines
pregnancy the risk is calculated per fetus (as around 90%
are dizygotic so have different karyotypes).
The DR for Down syndrome may be lower in twin
compared with singleton pregnancy1 . However, a recent
meta-analysis reported similar performance (89% for
singletons, 86% for dichorionic twins and 87% for monochorionic twins, at a false-positive rate (FPR) of 5%)22
(EVIDENCE LEVEL: 2++).
The likelihood of being offered invasive testing on the
basis of a combined screening result is greater in twin
compared with singleton pregnancy1 . Moreover, invasive
testing carries greater risks in twins23 25 . A meta-analysis
showed that the overall pregnancy loss rate following
chorionic villus sampling (CVS) in twin pregnancy was
3.8%, and following amniocentesis was 3.1%23 . Other
research has reported lower loss rates: 2% following CVS
and 1.52% following amniocentesis26 . The risk was
found to be similar for transabdominal and transcervical
approaches, use of a single-needle or double-needle system, and single or double uterine entry23 (EVIDENCE
LEVEL: 2++).
Screening and diagnostic testing for trisomy is more
complex in twin compared with singleton pregnancy. It
is important, therefore, that counseling prior to testing
is provided by healthcare professionals with expertise in
this area1 . It is important to inform women and their
partners in advance of the potentially complex decisions
that they will need to make on the basis of the results of
combined screening, bearing in mind the increased risk of
invasive testing in twins, the possible discordance between
dichorionic twins for fetal aneuploidy, and the risks of
selective fetal reduction1 (EVIDENCE LEVEL: 2+).
Cell-free DNA (cfDNA) analysis of maternal blood for
risk assessment for fetal trisomy 21 is used increasingly
in clinical practice. It has the potential to overcome many
of these complex issues, because it has a much higher DR
and lower FPR than does the combined test27 . In a recent
meta-analysis, the weighted pooled DR for trisomy 21 in
singleton pregnancy was 99% for a FPR of 0.1%28 . The
corresponding values in twin pregnancy were 94.4% and
0%. However, so far, the reported number of trisomy-21
cases in twin pregnancy diagnosed using cfDNA testing is
far smaller than that in singleton pregnancy (EVIDENCE
LEVEL: 2++).
251
the position of the twins within the uterus. During amniocentesis in monochorionic twins, if monochorionicity has
been confirmed before 14 weeks gestation and the fetuses
appear concordant for growth and anatomy, it is acceptable to sample only one amniotic sac. Otherwise, both
amniotic sacs should be sampled because of the possibility
of rare discordant chromosomal anomalies in monochorionic pregnancy. CVS in monochorionic pregnancy will
sample only the single placenta so will miss these rare discordant chromosomal anomalies. Discordance for most
of the common human aneuploidies (trisomies 13, 18 and
21, Turner syndrome and triploidy) has been reported in
monochorionic twin pairs30 . In the event of heterokaryotypic monochorionic pregnancy, selective reduction by
umbilical cord occlusion can be offered from 16 weeks
onwards, with a survival rate of more than 80% for the
healthy twin31,32 . When monochorionic twins are discordant for an abnormality, prior to invasive testing a
discussion should take place regarding the complexity
of selective termination, should it become necessary32
(EVIDENCE LEVEL: 3).
ISUOG Guidelines
252
compared with 4% in pregnancies with CRL discordance < 10%40 . However, CRL discordance at 7 + 0 to
9 + 6 weeks gestation is a predictor of the risk of single
fetal demise in the first trimester (DR of 74% for a FPR
of 5%)41 (EVIDENCE LEVEL: 2++).
ISUOG Guidelines
demise of the affected twin while protecting the healthy
twin against losing part of its circulating blood volume
into the terminated twin following its death. The survival
rate of the cotwin is approximately 80% and the risk of
premature rupture of the membranes and preterm birth
prior to 32 weeks is 20%49 . The risk of adverse neurological sequelae in the surviving cotwin may also be increased
compared with that in uncomplicated pregnancy49 52
(EVIDENCE LEVEL: 2++).
253
ISUOG Guidelines
254
EFW discordance between twins is significantly associated with the risk of perinatal loss69 . The hazard ratio
for the risk of total perinatal loss in twins with an EFW
discordance 25% was found to be 7.3. According to
the National Institute for Health and Care Excellence
guidance, EFW discordance should be calculated and
documented at every scan from 20 weeks onwards. If
this discordance reaches 25% or more, a referral should
be made to a tertiary-level fetal medicine unit for assessment, increased fetal surveillance, including fetal Doppler,
and planning of delivery when appropriate1 (EVIDENCE
LEVEL: 2++).
Classification of monochorionic twin pregnancy
complicated by sFGR
Classification of sFGR in monochorionic twins depends
on the pattern of end-diastolic velocity at umbilical
artery Doppler (GOOD PRACTICE POINT).
The classification of sFGR depends on the pattern of
end-diastolic velocity in the umbilical artery (Figure 4)70 .
In Type I, the umbilical artery Doppler waveform has
positive end-diastolic flow. In Type II, there is absent or
reversed end-diastolic flow (AREDF). In Type III, there
is a cyclical/intermittent pattern of AREDF. The survival
rate in Type-I sFGR is greater than 90% (in-utero mortality rates of up to 4%). Type-II sFGR is associated with
a high risk of IUD of the growth-restricted twin and/or
very preterm delivery with associated risk of neurodevelopmental delay if the other twin survives (IUD of either
twin in up to 29% and risk of neurological sequelae in up
to 15% of cases born prior to 30 weeks). Type-III sFGR
is associated with a 1020% risk of sudden death of
the growth-restricted fetus, which is unpredictable (even
in cases in which ultrasound features have been stable).
There is also a high (up to 20%) associated rate of
Type 1
Type 2
Type 3
Figure 4 Classification of selective fetal growth restriction in monochorionic twin pregnancy. In Type I, the umbilical artery Doppler
waveform has positive end-diastolic flow, while in Type II there is absent or reversed end-diastolic flow (AREDF). In Type III there is a
cyclical/intermittent pattern of AREDF.
ISUOG Guidelines
If there is a substantial risk of fetal demise of one
cotwin before 26 weeks, selective termination may be
considered (GRADE OF RECOMMENDATION: D).
In monochorionic twin pregnancy complicated by
sFGR, fetal growth should be assessed at least every 2
weeks, and fetal Doppler (umbilical artery and MCA) at
least weekly. If the umbilical artery Doppler is abnormal,
assessment of the DV blood flow should be undertaken.
The aim in managing these pregnancies is to prolong the
pregnancy at least until viability is achieved, while at the
same time avoiding single IUD with its associated serious
consequences for the surviving cotwin. In dichorionic twin
pregnancy complicated by sFGR, follow-up visits could
be less frequent, as delivery is usually not recommended
before 3234 weeks gestation.
In cases in which Doppler assessment concludes that
there is a real risk of fetal demise of one twin before 26
weeks of gestation, the option of selective termination
should be explored in order to protect the normally grown
fetus from serious harm should the smaller twin die in
utero. Management of these cases is complex and should
be coordinated by a tertiary-level fetal medicine center72
(EVIDENCE LEVEL: 2).
The timing of delivery should be decided based on
assessment of fetal wellbeing, interval growth, biophysical
profile, DV waveform and/or computerized cardiotocography (CTG), when available. However, as the risk of
IUD in these pregnancies is increased, delivery might be
indicated even before abnormalities in the DV Doppler
or the computerized CTG become evident. Furthermore,
the incidence of severe cerebral injury in monochorionic
twins complicated by sFGR is approximately 10% and is
associated with abnormal umbilical artery Doppler, single
IUD and low gestational age at birth73 . Interestingly, the
risks of neonatal morbidity (38% vs 19%), particularly
respiratory distress syndrome (32% vs 6%) and cerebral lesions, are higher in the larger than in the smaller
cotwin74 (EVIDENCE LEVEL: 2++).
255
ISUOG Guidelines
256
Staging of TTTS
Classification
Polyhydramniosoligohydramnios sequence:
DVP > 8 cm in recipient twin and DVP < 2 cm in
donor twin
Bladder in donor twin not visible on ultrasound
Absent or reversed umbilical artery diastolic flow,
reversed ductus venosus a-wave flow, pulsatile
umbilical venous flow in either twin
Hydrops in one or both twins
Death of one or both twins
II
III
IV
V
ISUOG Guidelines
257
ISUOG Guidelines
258
frequency and mode of surveillance have yet to be established. The incidence of TAPS occurring spontaneously in
MCDA twins is up to 5%. However, it may complicate
up to 13% of cases of TTTS following laser ablation96 .
TAPS is believed to be due to the presence of miniscule
arteriovenous anastomoses (< 1 mm) which allow slow
transfusion of blood from the donor to the recipient,
leading to highly discordant hemoglobin concentrations
at birth (EVIDENCE LEVEL: 3). The postnatal diagnosis
of TAPS is made based on the finding of chronic anemia
(including reticulocytosis) in the donor and polycythemia
in the recipient. The criteria for diagnosis include a difference in hemoglobin concentration between the twins
of more than 8 g/dL and at least one of either reticulocyte
count ratio greater than 1.7 or small vascular anastomoses
(< 1 mm in diameter) in the placenta109,110 The prenatal
diagnosis of TAPS is based on the finding of discordant
MCA Doppler abnormalities, including MCA-PSV > 1.5
multiples of the median (MoM) in the donor, suggesting
fetal anemia, and MCA-PSV < 1.0 MoM in the recipient,
suggesting polycythemia. Additional ultrasound findings
in TAPS include differences in placental echogenicity and
thickness, with a bright, thickened section associated
with the donor and an echolucent thin section associated with the recipient. The polycythemic twin might
have a starry sky appearance of the liver pattern due
to diminished echogenicity of the liver parenchyma and
increased brightness of the portal venule walls. The antenatal and postnatal severity-based staging classifications
are shown in Table 2 109,110 (EVIDENCE LEVEL: 3).
The outcome of twin pregnancies complicated by TAPS
is variable. Severe TAPS may result in IUD of both twins.
At the other end of the spectrum, mild TAPS may still
allow the birth of two healthy neonates (apart from
Stage
Antenatal staging
4
5
Postnatal staging:
intertwin
Hb diff (g/dL)
> 8.0
> 11.0
> 14.0
> 17.0
> 20.0
ISUOG Guidelines
259
Figure 5 (a) Mid-sagittal ultrasound image of pump twin in a pregnancy affected by twin reversed arterial perfusion (TRAP) sequence.
(b,c) Sagittal views of TRAP mass. (d) Intrafetal laser treatment as a means to arrest the flow in the TRAP mass. The needle is positioned,
under ultrasound guidance, in the TRAP mass near the cord insertion.
ISUOG Guidelines
260
5%, respectively128 (EVIDENCE LEVEL: 3). The recommended timing of delivery varies from 32 to 36 weeks
gestation. Recent evidence suggests that MCMA twin
pregnancies are at increased risk of IUD compared with
other types of twin pregnancy and should be delivered by
Cesarean section between 32 and 34 weeks of gestation
(EVIDENCE LEVEL: 3). This is based on the finding that,
after 32 + 4 weeks gestation, the risk of IUD is greater
in ongoing MCMA pregnancy compared with the risk of
non-respiratory neonatal complications when the twins
are delivered129 . Therefore, individualized assessment of
these pregnancies should inform the timing of delivery.
It is important to realize that umbilical cord entanglement is present in almost all monoamniotic twins evaluated systematically by ultrasound and color Doppler130 .
A systematic review including a total of 114 monoamniotic twin sets (228 fetuses) with cord entanglement
concluded that cord entanglement does not contribute to
prenatal morbidity and mortality in monoamniotic twin
pregnancy127 . Moreover, the presence of an umbilical
artery notch, without other signs of fetal deterioration, is
not indicative of an adverse perinatal outcome131 (EVIDENCE LEVEL: 2).
In MCMA twin pregnancies undergoing selective reduction (because of discordant anomaly, TRAP sequence,
severe TTTS or sFGR), cord occlusion and transection are
recommended to prevent fetal demise of the other twin
due to cord accidents132 135 . The perinatal outcomes are
similar to those of discordant MCDA twins treated with
cord occlusion. However, the rate of preterm prelabor
rupture of the membranes is higher and gestational age
at delivery is lower in MCMA than in MCDA pregnancy
(EVIDENCE LEVEL: 3).
Conjoined twins
Conjoined twins are very rare, occurring in approximately 1 in 100 000 pregnancies (1% of monochorionic
twin pregnancies). Conjoined twins are always MCMA
twin pregnancies. Diagnosis with ultrasound in the first
trimester is now the norm (on visualizing close and fixed
apposition of the fetal bodies, with fusion of the skin
lines at some point). A recent series of 14 cases from a
single referral center reported that, following diagnosis,
20% of parents opted for termination and 10% of fetuses
died in utero. Among those opting to continue the pregnancy, survival to discharge was only around 25%, and
the majority of these had significant morbidity136 .
The classification of conjoined twins depends on the site
of the union. The most common form is thoracopagus,
in which the twins face each other and have junctions
between chest and abdomen, often with conjoined livers,
hearts and intestinal structures136 .
In ongoing pregnancies, detailed expert ultrasound
imaging (with or without MRI) is important in order to
detail the cardiovascular (and other) anatomy of the twins
as far as possible prior to delivery. Although vaginal delivery of conjoined twins has been reported, there is a significant risk of obstructed labor, dystocia and uterine rupture,
GUIDELINE AUTHORS
A. Khalil, Fetal Medicine Unit, St Georges Hospital, St
Georges University of London, London, UK
M. Rodgers, Centre for Reviews and Dissemination, University of York, UK
A. Baschat, The Johns Hopkins Center for Fetal Therapy,
Baltimore, MD, USA
A. Bhide, Fetal Medicine Unit, St Georges Hospital, St
Georges University of London, London, UK
E. Gratacos, Fetal Medicine Units and Departments of
Obstetrics, Hospital Clinic-IDIBAPS, University of
Barcelona, Barcelona, Spain
K. Hecher, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany
M. D. Kilby, Centre for Womens and Childrens
Health, University of Birmingham and Fetal Medicine
Centre, Birmingham Womens Foundation Trust, Birmingham, UK
L. Lewi, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
K. H. Nicolaides, Harris Birthright Research Centre for
Fetal Medicine, Kings College Hospital, London, UK
D. Oepkes, Division of Fetal Medicine, Department of
Obstetrics, Leiden University Medical Center, Leiden,
The Netherlands
N. Raine-Fenning, Division of Child Health, Obstetrics
and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
K. Reed, Twin and Multiple Births Association (TAMBA)
L. J. Salomon, Hopital Necker-Enfants Malades, AP-HP,
Universite Paris Descartes, Paris, France
A. Sotiriadis, Department of Obstetrics and Gynaecology,
Aristotle University of Thessaloniki, Thessaloniki, Greece
B. Thilaganathan, Fetal Medicine Unit, St Georges Hospital, St Georges University of London, London, UK
Y. Ville, Hospital Necker-Enfants Malades, AP-HP, Universite Paris Descartes, Paris, France
CITATION
These Guidelines should be cited as: Khalil A, Rodgers
M, Baschat A, Bhide A, Gratacos E, Hecher K, Kilby
MD, Lewi L, Nicolaides KH, Oepkes D, Raine-Fenning
N, Reed K, Salomon LJ, Sotiriadis A, Thilaganathan B,
Ville Y. ISUOG Practice Guidelines: role of ultrasound
in twin pregnancy. Ultrasound Obstet Gynecol 2016; 47:
247263.
ISUOG Guidelines
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